This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic 06-AT-101: In this project, we propose two project areas based on the use of Magnetic Resonance Imaging modalities at both the cerebral (brain) and sub-cerebral (spinal) levels. Our first project area is to assess and compare the dose-response relationships of mindfulness and compassion meditation, studying subjects that are part of a large (N=360) research trial (NIH 1R01AT004698-01) beginning at Emory University. In the present proposal, we will longitudinally assess the trainees in the Emory study at pre-training and post-training stages by measuring changes in brain activation (fMRI) and structure (e.g. cortical thickness) measures that have previously been developed and applied to more advanced meditation practitioners at Massachusetts General Hospital. The second project area is to perform the first MRI exploration of the nature of bodily states of awareness that are traditionally reported in conjunction with advanced yoga meditation practices, such as Tibetan gTummo meditation. Here, we will use three-dimensional high resolution MRI based thermometry to accurately measure changes in internal body temperature, particularly in the region of the spinal cord, following meditation practices which are traditionally viewed as causing such changes. Together, these cerebral and sub-cerebral MRI imaging studies will provide important insight into the physiological and anatomical changes associated over time with two standard meditation protocols that are already in widespread use for stress reduction (mindfulness and compassion), and one more advanced protocol (gTummo) which so far has received little study but which is considered fundamental to more advanced practices. PUBLIC HEALTH RELEVANCE: The increasing use of meditation as a treatment for a variety of stress-related medical conditions highlights the public health importance of identifying mechanisms by which meditation may improve health, both to confirm efficacy for this widely used intervention and to better identify disease states toward which meditation might be optimally applied. The proposed study will test the hypothesis that meditation reduces stress- related inflammatory responses via reductions in autonomic activation in the face of perceived psychosocial stress. If confirmed, the long-term health implications of this hypothesis are far reaching, given evidence that activation of innate immune inflammatory pathways represents an important mechanism by which stress promotes and/or worsens a wide range of serious medical and psychiatric conditions (i.e. vascular disease, diabetes, cancer, HIV, major depression) to which meditation is being increasingly applied as an intervention.